| 1. |
- Blomström-Lundqvist, Carina, et al.
(författare)
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Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation : The CAPTAF Randomized Clinical Trial
- 2019
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Ingår i: JAMIA Journal of the American Medical Informatics Association. - Chicago : American Medical Association (AMA). - 1067-5027 .- 1527-974X .- 0098-7484 .- 1538-3598. ; 321:11, s. 1059-1068
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. OBJECTIVE To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or beta-blocker, with 4-year follow-up. Study dateswere July 2008-September 2017. Major exclusionswere ejection fraction <35%, left atrial diameter > 60 mm, ventricular pacing dependency, and previous ablation. INTERVENTIONS Pulmonary vein isolation ablation (n= 79) or previously untested antiarrhythmic drugs (n= 76). MAIN OUTCOMES AND MEASURES Primary outcomewas the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. RESULTS Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P=.003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8%[95% CI, -12.9% to -0.7%]; P=.03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. CONCLUSIONS AND RELEVANCE Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.
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| 2. |
- Gizurarson, Sigfus, et al.
(författare)
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358 Effects of complete heart block on myocardial function; morphology and energy metabolism in rat model
- 2007
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Ingår i: European Journal of Heart Failure Supplements. ; 6:Supplement 1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Severe sustained bradycardia may cause acute and possibly even chronic congestive heart failure (CHF). The aims of this study were: a) to set up a small-animal model of complete heart block (CHB) in rats, and b) to investigate acute and chronic effects of CHB on cardiac function, morphology and energy metabolism Methods: CHB was induced in 6 male Sprague-Dawley rats (∼ 250 g) by means of electrocautery applied to the region of AV node and were compared to controls (n=15). The rats were investigated 1, 3 and 12 weeks after induction of CHB with transthoracic ultrasound. After 12 weeks the animals were anesthetized and intubated. The chest was opened and right respectively left ventricular pressure curves were obtained. After the sacrifice, the hearts were freeze-clamped for analysis of myocardial creatine, adenine nucleotides, catecholamines and intracellular lipids. Results: The efficacy of operative procedure was 100%. The perioperative mortality rate was 20%. While heart rate was decreased by ∼ 50% (p < 0.01), stroke volume doubled (p < 0.01) in the CHB rats. Cardiac index remained unchanged. The rats with CHB grew normally and were in no apparent distress. Filling pressures in left and right ventricle were normal. The CHB rats developed cardiomegaly with biventricular dilatation and hypertrophy with markedly increased left ventricular mass (LV) (p < 0.01). There was no change in the myocardial content of creatine and adenine nucleotides. Conclusions: Rats with CHB are compensating for reduction in heart rate with dramatically increased stroke volume without hemodynamical signs of heart failure even after prolonged period of time. Markedly increased LV mass is probably due to volume overload but is not associated with metabolical derangement as seen in other forms of pathologic LV hypertrophy. This model may be useful to study the effects of severe bradycardia on myocardial structure, function, electrophysiology and metabolism as well as for different aspects of LV hypertrophy. Similarly, the model may be useful for studies of cell therapy for reparation of AV node.
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| 3. |
- Gizurarson, Sigfus, et al.
(författare)
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Atrial fibrillation in patients admitted to coronary care units in western Sweden - focus on obesity and lipotoxicity.
- 2015
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 48:5, s. 853-60
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) is the most common form of arrhythmia in humans and is associated with substantial morbidity and mortality. Obesity and diabetes have been linked to myocardial lipotoxicity - a condition where the heart accumulates and produces toxic lipid species. We hypothesized that obesity and diabetes were involved in the pathophysiology of AF by means of promoting a lipotoxic phenotype in atrial muscle, and that AF predicts mortality in cardiac care patients.
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| 4. |
- Gizurarson, Sigfus, et al.
(författare)
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Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat.
- 2007
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Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1099-5129. ; 9:6, s. 411-6
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Tidskriftsartikel (refereegranskat)abstract
- Severe sustained bradycardia may cause acute and possibly chronic congestive heart failure (CHF). The aim of this study was to investigate acute and chronic effects of complete heart block (CHB) on cardiac function, morphology, and creatine (Cr) metabolism.
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| 5. |
- Gizurarson, Sigfus, et al.
(författare)
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Electrophysiological Effects of Lysophosphatidylcholine on HL-1 Cardiomyocytes Assessed with a Microelectrode Array System
- 2012
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Ingår i: Cellular Physiology and Biochemistry. - : S. Karger AG. - 1015-8987 .- 1421-9778. ; 30:2, s. 477-488
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sudden death due to malignant ventricular arrhythmias is the most important cause of death in acute myocardial infarction. Improved knowledge about the pathophysiology underlying these arrhythmias is essential in the search for new anti-arrhythmic strategies. Lysophosphatidylcholine (LPC), a hydrolysis product of (membrane) phospholipid degradation, is one of the most potent pro-arrhythmic substances that accumulate in the human heart during myocardial ischemia. The aim of this study was to set up and validate an in vitro experimental system for studies on the effects of LPC on electrophysiological parameters in beating cardiomyocytes. Methods and Results: Spontaneously beating HL-1 cardiomyocytes were cultured on multielectrode array microchips for three days for the recording of electrical activities in the form of field potentials (FP). FPs were recorded at baseline and after addition of 2, 4, 8, 12, 16, 20, and 24 mu M of LPC to the cell medium (n=9). We found that LPC could induce rapid effects on electrical parameters in the HL-1 cells. The overall half-maximal effective concentration (EC50) of LPC was around 12 mu M. The beating rate and peak-peak amplitude of FP thus decreased at concentrations >= 12 mu M and were inversely proportional to increased LPC concentration. The duration of FP was significantly prolonged with LPC above 12 mu M and was concentration-dependent. LPC delayed signal propagation, an effect which was mimicked by blocking gap junctions with heptanol and attenuated by pre-treatment with isoprenaline and atropine. Finally, asynchronous activity was induced by LPC at >12 mu M. Conclusions: LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our in vitro model with HL-1 cells and microelectrode array system may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts. Copyright (C) 2012 S Karger AG, Basel
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| 6. |
- Gizurarson, Sigfus
(författare)
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Metabolic aspects of cardiac arrhythmias
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiac arrhythmias are an important cause of mortality and morbidity in patients with cardiac diseases. Sudden death due to ventricular tachycardia and fibrillation (VT/VF) in the setting of acute myocardial infarction (AMI) and heart failure (HF) is a frequent cause of premature death. Another recognized cause for sudden cardiac death is acquired complete heart block (CHB), a condition where the heart must quickly adapt to volume overload and increased wall stress to maintain normal hemodynamics. In the pre-pacemaker era this was a condition with a very high mortality mostly due to sudden death and progressive HF. The most common sustained arrhythmia, atrial fibrillation causes significant morbidity and is associated with stroke, heart failure and risk of premature death. The heart is an electro-mechanic pump that metabolizes mostly fatty acids for energy generation. Most of the energy is fuelling contractile work but approximately one-third is designated for ion pumps that maintain the electrochemical homeostasis of the cardiomyocyte, and give rise to the cell depolarization and repolarization. As the ATP pool is completely turned over every 10s, effective metabolism is imperative for the maintenance of electrical stability in the cell. In different pathophysiological states, i.e. obesity and diabetes, there is a mismatch between uptake and utilization of fatty acids leading to intracellular lipid accumulation. This may lead to the production of toxic lipid metabolites (e.g. lysophosphatidylcholine (LPC), diacylglycerol (DAG) and ceramides) and is referred to as lipotoxicity. LPC is also generated during myocardial ischemia and has been proposed as a contributor to the generation of ventricular arrhythmias during AMI. An import metabolic regulatory hormone, growth hormone (GH), has been shown to exert various positive effects in post-infarction HF. Aims I. To evaluate the short- and long-term effects of CHB on cardiac function, morphology and energy metabolism in the rat II. To investigate the effects of GH on ischemic and non-ischemic arrhythmogenesis in the rat III. To set up and validate an in vitro experimental system for studies of the effects of LPC on electrophysiological parameters in beating cardiomyocytes. IV. To evaluate associated risk factors for having AF in patients admitted to cardiac care units and to evaluate the role of lipid metabolism in the pathophysiology of AF. Results and conclusions I. Rats with CHB compensate for the reduction in heart rate by doubling the stroke volume and thereby maintaining cardiac output. Increases in wall tension leads to eccentric left ventricular hypertrophy. After long-term CHB there were no hemodynamic or metabolic signs of HF. II. GH reduced the occurrence of spontaneous VT/VF in rats with induced AMI as well as reducing induced VT/VF in anesthetized rats. This adds to previously described beneficial effects of GH in HF and AMI, and we suggest that the effect is partly mediated via decreased sympathetic stimulation. III. LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our model may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts. IV. In a multivariate analysis we found that obesity was associated with AF, but diabetes was not. AF was associated with quantitative and qualitative alterations in atrial lipid content but not with signs of lipotoxicity. Polyunsaturated DAG may play a role in pathophysiology of AF.
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| 7. |
- Råmunddal, Truls, 1973, et al.
(författare)
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Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology.
- 2008
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 41:2, s. 144-51
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Tidskriftsartikel (refereegranskat)abstract
- A growing body of evidence suggests a possible role for growth hormone (GH) in the treatment of congestive heart failure (CHF) and myocardial infarction (MI). The aim of this study was to investigate in vivo the effects of GH treatment on incidence and severity of ventricular arrhythmias normal and MI rats.Male Sprague-Dawley rats weighing approximately 350 g were randomized into 3 groups. Growth hormone-treated rats (n = 6) received 6 mg/kg of human GH. The placebo group (n = 10) received 1 mL of saline. Amiodarone-treated rats (n = 10) were injected with 25 mg/kg and served as positive controls. All animals received a single intraperitoneal injection 6 hours before induction of MI. Myocardial infarction was induced by ligation of the left coronary artery, resulting in a large (approximately 40%) anterolateral MI. A computerized electrocardiographic tracing was obtained continuously before induction of MI and up to 1 hour postinfarction. Invasive hemodynamics including intraventricular and arterial pressure were registered for 60 minutes post-MI. Qualitative as well as quantitative variables of ventricular arrhythmias were analyzed. Invasive electrophysiology with pacing in right atrium and ventricle was performed in normal rats (control, n = 13; GH, n = 6; amiodarone, n = 6) to asses inducibility of supraventricular and ventricular arrhythmias.Growth hormone- and amiodarone-treated rats had lower resting heart rate at baseline before induction of MI. The arrhythmia scores in the GH- (3.8 +/- 1) and amiodarone-treated (3.9 +/- 0.5) animals were significant lower than in the placebo group (5.9 +/- 0.5, P < .05). There was no significant difference in arrhythmia score between the GH and amiodarone groups. The incident of inducible ventricular arrhythmias was lower in the GH (2/6, 33%) and amiodarone (2/6, 33%) groups compared with controls (13/16, 81%; P = .05). There was no difference in inducibility of atrial fibrillation between the GH (5/6, 83%) and control (13/14, 93%) groups, whereas the inducibility of atrial fibrillation was significantly lower in the amiodarone group (2/6, 33%; P < .05).Pretreatment with GH reduces the burden of ventricular arrhythmias in rats with postinfarction CHF due to acute MI. Growth hormone may be useful in the treatment of CHF and acute MI.
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| 8. |
- Shao, Yangzhen, 1981, et al.
(författare)
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Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology.
- 2014
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Ingår i: Molecular and cellular biochemistry. - : Springer Science and Business Media LLC. - 1573-4919 .- 0300-8177. ; 393:1-2, s. 191-197
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Tidskriftsartikel (refereegranskat)abstract
- Arrhythmias have been treated for a long time with drugs that mainly target the ionic pumps and channels. These anti-arrhythmic regimens per se introduce new arrhythmias, which can be detrimental to patients. Advances in development of novel pharmacology without introduction of iatrogenic arrhythmias are thus favorable for an effective treatment of arrhythmias. Electrophysiological stability of the heart has been shown to be closely associated with cardiac metabolism. The present effective anti-arrhythmic drugs such as beta-blockers and amiodarone have profound beneficial effects in regulating myocardial metabolism. Aiming at decreasing production of toxic metabolites or preventing accumulation of arrhythmogenic lipids perhaps is a good strategy to effectively control arrhythmias. Therefore, a better understanding of the pro-arrhythmic profiles of cardiac metabolites helps to explore a new generation of metabolically oriented anti-arrhythmic medications. In this review, we present several lipid metabolites and summarize their arrhythmogenic characteristics.
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